Pheromones are chemicals released by an organism into its environment enabling it to communicate with other members of its own species. Mealybugs are known to spoil crops such as grapes, pears etc., especially the long-tailed mealybug. The long-tailed mealybug is scientifically known as Pseudococcus longispinus (Targioni-Tozzetti).
The racemic form of the pheromone was prepared synthetically by the Miller group after identifying the structure of isolated pheromone. Miller group has reported that 25 μg is sufficient to attract male mealybugs for three months and they can be trapped and killed; male population is thus decreased.
Pheromones play an important role in chemical communication among organisms. Various chiral and non-racemic pheromones have been identified since the late 1960s. Their enantioselective syntheses were achieved so as to establish the absolute configuration of the naturally occurring pheromones and also to clarify the relationship between absolute configuration and the bioactivity of the chiral pheromones. Synthesis of pheromones is an important and arising field of research to establish the structures and also to provide sufficient material to carry out biological studies. In general, natural pheromones are available in very limited quantities (usually in μg by killing several bugs) which restrict the extensive field trials. To overcome such constrain several methods have been reported in the literature to construct low molecular weight pheromones.
Article titled “Sex pheromonal activity of (+)-bornyl acetate and related compounds to the American cockroach” by Manabe S et al. published in Journal of Chemical Ecology, 1983; 9(3), pp 433-48 reports many compounds related to (+)-bornyl acetate (a sex pheromone mimic of the American cockroach) were synthesized and tested for sex pheromonal activity. All compounds except for esters of (+)- and (−)-borneol were inactive, whereas (+)-bornyl acetate (Ib) and propionate (Ic) showed the activity at 0.05 mg. Although (−)-bornyl propionate (IVc) is the enantiomer of Ic, it exhibited weak activity at 0.5 mg dose. On the basis of the behavioral assay results, important chemical factors in Ib for pheromonal activity were elucidated and are discussed in connection with another mimic, (+)-trans-verbenyl acetate. The M/F ratio index in EAG was evaluated for both active and inactive compounds. The index demonstrated a good correlation with the behavioral activity.
Article titled “Syntheses and determination of absolute configurations and biological activities of the enantiomers of the long-tailed mealybug pheromone” by Remya Ramesh et al. published in Journal of Organic Chemistry, 2013, 78, pp 6281-6284 reports preparation and assignment of absolute configurations to both enantiomers of the sex pheromone of the long-tailed mealybug, an irregular monoterpenoid with extraordinary biological activity. Comparison of the biological activities of both enantiomers and the racemate in field trials showed that the (S)-(+)-enantiomer was highly attractive to male mealybugs, strongly suggesting that female long-tailed mealybugs produce this enantiomer. The (R)-(−)-enantiomer was benign, being neither attractive nor inhibitory. Article titled “Synthesis of Verbenols and related alcohols and their pmr spectra with shift reagent” by Chikao Nisiuno et al. published in Agricultural and Biological Chemistry, 1979, 43 (9), pp 1967 1974 reports (+)-bornyl acetate (bicydicmonoterpenoid) and three other plant-derived compounds excite males of the American cockroach showing the typical sexual response mentioned.
Article titled “Useful Reactions in Modern Pheromone Synthesis” by Mori et al. published in Current Organic Synthesis, 2004, 1, pp 11-29 disclosed various aspects of pheromone synthesis where methodologies such as organoborane reactions, organotransition metal chemistry including olefin metathesis, asymmetric epoxidation, asymmetric dihydroxylation and other asymmetric chemical processes was demonstrated.
Article titled “The Baeyer-Villiger oxidation of aldehydes and ketones” by C. H. Hassall published in book titled “Organic Reactions” 2011, reports Baeyer and Vlliger showed that the oxidation of alicyclic ketones, menthone, tetrahydrocarvone, and camphor with permono-sulfuric acid led to the formation of lactones.
Article titled “Chemoselective reductive deoxygenation of α,β-unsaturated ketones and allyl alcohols” by Adusumilli Srikrishna et al. published in Tetrahedron Letters, 1995, 36 (13), pp 2347-2350 reports a simple and convenient procedure for a highly chemoselective reductive deoxygenation of α,β-unsaturated ketones and allyl alcohols to olefins by sodium cyanoborohydride and boron trifluorideetherate in dry THF.

Article titled “Pyridiniumchlorochromate. An efficient reagent for oxidation of primary and secondary alcohols to carbonyl compounds” by E. J. Corey et al. published in Tetrahedron Letter, 1975, 16, pp 2647-2650 reports pyridiniumchlorochromate is a readily available, stable reagent, that oxidizes a wide variety of alcohols to carbonyl compounds with high efficiency.

Article titled “Mechanisms of lactone hydrolysis in acidic conditions” by Rafael Gómez-Bombarelli et al. published in Journal of Organic Chemistry, 2013, 78 (14), pp 6880-6889 reports the acid-catalyzed hydrolysis of linear esters and lactones was studied using a hybrid supermolecule-polarizable continuum model (PCM) approach including up to six water molecules. The compounds studied included two linear esters, four β-lactones, two γ-lactones, and one δ-lactone: ethyl acetate, methyl formate, β-propiolactone, β-butyrolactone, β-isovalerolactone, diketene (4-methyleneoxetan-2-one), γ-butyrolactone, 2(5H)-furanone, and δ-valerolactone.
Article titled “Lanthanoids in organic synthesis. 6. Reduction of alpha-enones by sodium borohydride in the presence of lanthanoid chlorides: synthetic and mechanistic aspects.” by Andre L. Gemal et al. published in Journal of American Chemical Society, 1981, 103 (18), pp 5454-5459 reports reduction of alpha-enones by sodium borohydride in the presence of lanthanoid chlorides.
Article titled “Reduction of ketones to hydrocarbons with triethylsilane: m-nitroethylbenzene” by James L. Fry et al. published in Organic Synthesis, 1981, 60, 108 et al. reports other carbonyl reduction methods include the familiar Clemmensen and Wolff-Kishner reactions. These are usually conducted for extended periods of time at elevated temperatures under strongly acidic or basic conditions, respectively. Mixed metal hydride-Lewis acid reagents constitute strong reducing systems that are often effective in the deoxygenation of diaryl ketones and some aryl alkyl ketones. However, even the mixed lithium aluminum hydride-aluminum chloride and sodium borohydride-boron trifluoride reagents reduce dialkyl ketones only to the corresponding alcohols, often with the formation of significant amounts of olefinic by-products.
Article titled “Acetic Anhydride” reports if the reaction is run at temperatures lower than 20° C., primary alcohols can be acetylated over secondary alcohols selectively. Under these conditions, tertiary alcohols are not acylated. Most alcohols, including tertiary alcohols, can be acylated by the addition of DMAP (4-Dimethylaminopyridine) and Acetyl Chloride to the reaction containing acetic anhydride and pyridine. In general, the addition of DMAP increases the rate of acylation by 104 (eq 2).

Article titled “Reduction Reactions” reports regioselective reduction of α,β-unsaturated carbonyl groups by luche reduction.
Article titled “Improved Synthesis of the Pheromone of the Long tailed Mealybug” by Jocelyn G. Millar et al. published in Synlett 2010, No. 15, pp 2319-2321 reports synthesis of pheromones involving Ireland-Claisen conditions in seven steps also discloses commercial development for detection, monitoring, and control of long-tailed mealybugs and the leafroll viruses that they vector.

In view of prior art, pheromones are usually obtained in μg to mg quantities which are insufficient for the determination of their absolute configuration as well as for the biological studies to examine their practicality in the field. Also in view of the technical constraints to scale up the material and cumbersome resolution, the present inventors have developed efficient synthesis for preparation of enantiomers of sex pheromones in good yields.